Potassium Carbonate → N-[(4-chlorophenyl)methyl]-7-(2-diethylaminoethyl)-2-(3-hydroxypropyl)-4-oxo-thieno[2,3-b]pyridine-5-carboxamide

HRID 2299300Notes

Reaction equation

HRID 2299300 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]([OH:23])=[C:12]3[CH:18]=[C:17]([CH2:19][CH2:20][CH2:21][OH:22])[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br.Br[CH2:34][CH2:35][N:36]([CH2:39][CH3:40])[CH2:37][CH3:38]>CN(C=O)C.Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[CH:18]=[C:17]([CH2:19][CH2:20][CH2:21][OH:22])[S:16][C:13]=3[N:14]([CH2:34][CH2:35][N:36]([CH2:39][CH3:40])[CH2:37][CH3:38])[CH:15]=2)=[O:9])=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 11430Potassium Carbonate2×HCID 706072-Bromoethyldiethylammonium bromide2×HCID 178522938HCID 178522938, compound

Product 1

HCID 6482398N-[(4-chlorophenyl)methyl]-7-(2-diethylaminoethyl)-2-(3-hydroxypropyl)-4-oxo-thieno[2,3-b]pyridine-5-carboxamideYield 19%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of N-(4-chlorobenzyl)4-hydroxy-2-(3-hydroxypropyl)thieno[2,3-b]pyridine-5-carboxamide (Example No. 8) (0.300 g) in DMF (4 mL) are added K2CO3 (0.550 g) and 2-bromo-N,N-diethylethylamine hydrobromide (0.623 g). The reaction is heated to 90° C. and stirred for 3 d. An additional 0.220 g of K2CO3 and 0.415 g of 2-bromo-N,N-diethylethylamine hydrobromide are added. The reaction is stirred at 90° C. for 6 h. The reaction mixture is concentrated in vacuo, and the resulting residue is partitioned between CH2Cl2 (25 mL) and H2O (25 mL). The aqueous layer is extracted with CH2Cl2 (3×25 mL). The combined organic layers are dried with MgSO4, filtered and concentrated in vacuo. The resulting yellow oil is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield a yellow oil. This material is dissolved in methanolic HCl and then concentrated in vacuo. The residue is recrystallized twice from ethyl acetate/methanol to yield 0.078 g (19%) of the title compound as an off-white, crystalline solid.

Workup

  1. stirringThe reaction is stirred at 90° C. for 6 h
  2. concentrationThe reaction mixture is concentrated in vacuo
  3. customthe resulting residue is partitioned between CH2Cl2 (25 mL) and H2O (25 mL)
  4. extractionThe aqueous layer is extracted with CH2Cl2 (3×25 mL)
  5. dry with materialThe combined organic layers are dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting yellow oil is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5)
  9. concentrationconcentrated in vacuo
  10. customto yield a yellow oil
  11. concentrationconcentrated in vacuo
  12. customThe residue is recrystallized twice from ethyl acetate/methanol

Sources & evidence

ORD record
ord-4a8945fa63c54ed1a5269a8de66e3b57
Source dataset
uspto-grants-2002_12
Patent number
US06495683B2

Reaction notes

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